目的 制备石杉碱甲渗透泵控释微丸,并探讨其在 Beagle 犬内的药动学特性。方法 采用挤出滚圆法制备渗透泵含药丸芯,以乙基纤维素和PEG400用量为考察因素结合星点设计效应面法优选包衣液处方,通过流化床包衣工艺制备石杉碱甲渗透泵控释微丸。按最优处方制备3批微丸并以累积释放度与时间进行零级、一级、Higuchi方程拟合考察其释药特性。以市售的石杉碱甲普通片为参比制剂,考察自制石杉碱甲渗透泵控释微丸的体内药动学特点,并比较两制剂的生物等效性。结果 微丸最优处方为PEG400用量10.5%,乙基纤维素用量61.5%,所制备的石杉碱甲渗透泵控释微丸24 h内释药具有零级释放特征,释放动力以渗透压为主。自制石杉碱甲渗透泵控释微丸的tmax与ρmax明显低于参比制剂,其t1/2比参比制剂延长约1倍,相对生物利用度为95.8%。结论 Hup-A渗透泵控释微丸在Beagle犬中有较好的缓释效果,体内相关性良好。
Abstract
OBJECTIVE To prepare huperzine A micro-porous osmotic pump pellets and to investigate the pharmacokinetic properties in Beagle dogs. METHODS The extrusion-spheronisation method was used to prepare the core of huperzine A pellets which then coated by fluid-bed coating technology.Central composite design-response surface method was used to optimize the prescription of coating layer.Then Zero-order, First-order and Higuchi equation of cumulative release with time were fitted to study its release characteristics.The commercially available huperzine A tablets were used as reference preparations to investigate the in vivo pharmacokinetics of huperzine A micro-porous osmotic pump pellets, and the bioequivalence of the two preparations were compared. RESULTS The formula of coating was optimized as followsEC of 61.5%, PEG400 of 10.5%. Zero-order kinetics existed in the release of the pellets in 24 h. Moreover, the osmotic pressure-controlled delivery was greatly responsible for drug release. In vivo study showed that tmax and ρmax of huperzine A micro-porous osmotic pump pellets were significantly lower than that of the reference preparation, and its t1/2 was significantly prolonged compared with the reference preparation, the relative bioavailability was 95.8%. CONCLUSION Huperzine A micro-porous osmotic pump pellets had a better sustained release effect in the Beagle dog and have a good correlation in vivo.
关键词
石杉碱甲 /
渗透泵控释微丸 /
星点设计效应面 /
零级释放 /
渗透压 /
累积释放度 /
药动学
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Key words
huperzine A /
micro-porous osmotic pump pellets /
central composite design-response surface method /
Zero-order release /
osmotic pressure /
in vitro accumulation release /
pharmacokinetics
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中图分类号：
R944
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参考文献
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脚注
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基金
浙江省神经精神疾病药物研究重点实验室资助项目(2019E10021);
浙江省医药卫生科技计划项目资助(2018KY349);
浙江省自然科学基金项目资助(LQY18H300002)
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